NCT02948348

Study to Nivolumab Following Preoperative Chemoradiotherapy

A Phase 1b/2 Multicenter Study to Investigate the Safety, Efficacy and Proof of Concept (POC) of Nivolumab Monotherapy as a Sequential Therapy Following Preoperative Chemoradiotherapy Patients With Locally Advanced Resectable Rectal Cancer

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Takayuki Yoshino · Academic / Other
• Sex: All
• Age: 20 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a phase Ib/II, open-label, single-arm, multicenter study to investigate the safety, efficacy, and proof of concept (POC) of monotherapy with nivolumab, an anti-PD-1 antibody drug, as a sequential therapy following chemoradiotherapy (CRT) with capecitabine and subsequent surgical therapy in patients with locally advanced resectable rectal cancer.

Detailed description

\[Phase Ib\] After preoperative CRT, to sequentially administer nivolumab in combination for patients with locally advanced resectable rectal cancer. To evaluate the safety of nivolumab in sequential combination therapy, the onset of dose-limiting toxicity (DLT) and the safety of subsequent surgical therapy, and to decide on a recommended dose (RD) for the phase II part. \[Phase II\] PhaseⅡ is composed of 4 cohorts. Cohort A: First-onset rectal cancer cohort (42 cases) To evaluate the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered following preoperative CRT. And to search for biomarkers related to therapeutic effects in first-onset cases. Evaluate the safety of surgical treatment. Cohort B: Rectal cancer with localized recurrence cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT. Search for biomarkers related to therapeutic effects in localized recurrence cases. Conduct an exploratory evaluation on the safety of surgical treatment. Cohort C: Rectal cancer with resectable lung/liver metastasis cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT. Search for biomarkers related to therapeutic effects in resectable lung/liver metastasis cases. Conduct an exploratory evaluation on the safety of surgical treatment. Cohort D: First-onset rectal cancer using ipilimumab-nivolumab combination cohort (25 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (240 mg/body at two-week intervals) and ipilimumab (1 mg/kg at six-week intervals) after preoperative CRT, and search for biomarkers related to therapeutic effects in first-onset cases. Conduct an exploratory evaluation on the safety of surgical treatment.

Conditions

• Cancer of Rectum

Interventions

Type	Name	Description
DRUG	Nivolumab	Capecitabine:Dose of 1650mg/m2,14days, Radiation:45Gy/25 fractions, Nivolumab :240mg on day1 of each cycle, Surgical therapy:The resection (LAR), intersphincteric resection (ISR), or abdominoperineal resection (APR).
DRUG	Ipilimumab	For only Cohort D,1 mg/kg at six-week intervals

Timeline

• Start date: 2016-10-01
• Primary completion: 2021-12-01
• Completion: 2022-08-01
• First posted: 2016-10-28
• Last updated: 2021-09-16

Locations

3 sites across 1 country: Japan